Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review

Abstract

Background: Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses.

Case presentation: We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed.

Conclusion: PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.

Keywords: Intraspinal metastasis; Invasive; Pituitary carcinomas; Prolactin-secreting pituitary adenomas; Recurrence; Refractory.

Fig. 1

Preoperative sagittal (A) and coronal (B) planes of magnetic resonance imaging (MRI) revealed a pituitary macroadenoma 2.5 cm*2.0 cm that invaded the right cavernous sinus and encased the right internal carotid artery (ICA) completely (Knosp grade 4). (C) and (D) Three months after the first transsphenoidal surgery (TSS), MRI indicated that the tumor was gross totally resected. (E) and (F) Before the first frontal craniotomy, MRI in October 2011 revealed a rapidly enlarged tumor with compression of the optic chiasm. (G) and (H) After the first frontal craniotomy, MRI demonstrated that the tumor was subtotally removed. (I) and (J) Before the second craniotomy, MRI in March 2012 indicated a rapidly growing tumor with compression of the optic chiasm and invasion into the third ventricle. (K) and (L) After the second frontal craniotomy, the tumor was subtotal resected

Fig. 2

(A) and (B) Before the first gamma knife radiosurgery (GKS) treatment, MRI in November 2012 reported that the tumor was located in the sellar and suprasellar regions. (C) and (D) Seven months after the first GKS treatment, MRI revealed that the tumor size was slightly decreased. (E) and (F) Before the second GKS treatment, MRI in November 2013 demonstrated that the tumor size increased significantly again (Knosp grade 4). (G) and (H) Eight months after the second GKS treatment, MRI in July 2014 indicated that the tumor size was reduced slightly

Fig. 3

(A) and (B) Before the third frontal craniotomy, the MRI in October 2014 demonstrated a rapid enlargement of the tumor with suprasellar extension and encasing the right ICA. (C) and (D) After the third craniotomy, the tumor was subtotally removed. (E) and (F) Before the fourth frontal craniotomy, MRI in January 2015 reported that the tumor volume increased significantly and compressed the optic chiasm. (G) and (H) After the fourth craniotomy, the tumor was subtotally resected. (I) and (J) MRI of the lumbar spine indicated an intradural extramedullary mass at the level of the fourth lumbar vertebra. (K) and (L) Postoperative MRI indicated that the intradural extramedullary lesions were completely resected

Fig. 4

Pathological results of the resected tumor samples. (A-C) Pathological findings from the third frontal craniotomy. (A) Mitotic activity was increased (HE: 20×). (B) Immunohistochemistry (IHC) of PRL in neoplastic cells was strongly positive (20×). (C) The Ki-67 index was increased to 10% (20×). (D-F) Pathological findings from the fourth frontal craniotomy. (D) Mitotic activity was increased (HE: 20×). (E) IHC of PRL in neoplastic cells was strongly positive (20×). (F) The Ki-67 index was increased to 20% (20×). (G-I) Pathological findings from resected intraspinal tumors. (G) Mitotic activity was increased (HE: 20×); (H) IHC of PRL in neoplastic cells was strongly positive (20×); (I) The Ki-67 index was increased to 30% (20×). H&E: hematoxylin-eosin; PRL: Prolactin